Human Immunodeficiency Virus (HIV) is a global health threat, likely to be controlled only by the development of an easily manufactured vaccine capable of eliciting strong humoral and cellular immune responses. Nodamura virus (NoV), a small positive-sense RNA virus, has many advantages for development as live vector vaccines, which are safer than attenuated or inactivated HIV vaccines, yet can elicit humoral and cellular immunity. As described in this proposal, NoV replicates to nearly the level of rRNA in the yeast S. cerevisiae, providing an inexpensive supply of RNA. A decade of hepatitis B vaccine production in yeast demonstrates the safety and cost-effectiveness of this organism. Recently, intramuscular immunization with in vitro transcribed recombinant Semliki Forest virus-derived naked RNA replicons has been shown to elicit significant levels of protection in mouse models of three economically important viruses. The goal of this pilot project is to develop an HIV vaccine based on a NoV RNA-derived, suicidal vector encoding HIV proteins. The novel feature of this proposal is that the RNA will be amplified in the yeast S. cerevisiae and introduced into mammals as naked RNA in yeast total RNA.We propose to do this by addressing the following specific aims: 1. To determine the immunologic effects of immunizing mice with yeast total RNA. 2. To characterize the replication and expression of viral RNA vectors encoding HIV genes in tissueculture. 3. To determine immunization routes, schedules, and viral RNA vector formulations that induce significant immune responses to HIV gene products in mice.